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Coupling Between GABA-A Receptor and Chloride Transporter Underlies Ionic Plasticity in Cerebellar Purkinje Neurons

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Abstract

Ionic plasticity, a form of synaptic plasticity unique to inhibitory neurotransmission, can be induced in cerebellar Purkinje neurons by brain-derived neurotrophic factor (BDNF). It is expressed as a decrease in synaptic strength of GABA-A transmission onto Purkinje neurons due to reduced transmembrane chloride gradient. By making whole-cell recordings, we found that the effect of BDNF is mediated by neuronal potassium and chloride transporter KCC2 because it is blocked by inhibitors of KCC2 or by raising the intracellular chloride concentration. Under these conditions in which KCC2 activity is reduced, BDNF augments evoked GABA-A currents suggesting a direct facilitatory effect of BDNF on GABA-A receptor. We also found that the effect of BDNF is highly localized at the GABA-A synapse and is secured by physical coupling between GABA-A receptor and KCC2, as revealed by coimmunoprecipitation studies. Based on these results, we hypothesize that the interaction between KCC2 and specific subunit of GABA-A receptor represents a fundamental mechanism rendering the rapid induction of ionic plasticity in individual or input-specific GABA synapses possible. Such a mechanism may be important for the function of Purkinje neurons that are known to express GABA-A receptors with different subunit compositions.

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Acknowledgments

This work was supported by the Research Grants Council of Hong Kong (2900336 and 2130203) and the NSFC/RGC Joint Research Scheme 30931160433 from the National Natural Science Foundation of China.

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Authors and Affiliations

  1. Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China

    Ying Huang

  2. Department of Biological Science and Technology, School of Life Sciences, Nanjing University, Nanjing, China

    Jian-Jun Wang

  3. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China

    Wing-Ho Yung

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  1. Ying Huang
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  2. Jian-Jun Wang
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  3. Wing-Ho Yung
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Correspondence to Wing-Ho Yung.

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Huang, Y., Wang, JJ. & Yung, WH. Coupling Between GABA-A Receptor and Chloride Transporter Underlies Ionic Plasticity in Cerebellar Purkinje Neurons. Cerebellum 12, 328–330 (2013). https://doi.org/10.1007/s12311-013-0453-3

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  • DOI: https://doi.org/10.1007/s12311-013-0453-3

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